Circadian rhythm-associated clinical relevance and Tumor Microenvironment of Non-small Cell Lung Cancer

Objective: We aimed to explore the prognostic implication for non-small cell lung cancer (NSCLC) based on the expression profiles of circadian clock-related genes (CCRGs), and describe the changes of immune infiltration and cell functions of related to the circadian rhythm. Methods: Univariate and multivariate Cox proportional hazard regression were performed to determine a CCRGs risk-score significantly correlated with overall survival (OS) of the training set and validation set. GO, KEGG, and GSVA indicated discrepant changes in cellular processes and signaling pathways associated with these CCRGs. Immune cell infiltration and mutation rates were investigated by the online analysis platform and the algorithm provided by works of literature. Results: The signature-based on ten-gene signatures could independently predict the OS both in TCGA lung adenocarcinoma (p < 0.001, HR: 1.228, 95% CI: 1.158 to 1.302) and lung squamous cell carcinoma (p < 0.001, HR: 2.501, 95% CI: 2.010 to 3.117), respectively. The circadian oscillations driven by CCRGs could disturb the metabolism and cellular functions of cancer cells. The infiltration level of critical cells in specific anti-tumor immunity process was suppressed apparently. In contrast, the infiltrating of inflammatory cells and immune cells with negative regulatory effects were promoted in the high-risk group. CCRGs were evolutionarily conserved with low mutation rates, which brought difficulties to explore therapeutic targets. Conclusion: We identified and validated a circadian rhythm signature to described clinical relevance and tumor microenvironment of NSCLC, which revealed that circadian rhythms might play an influential role in the NSCLC.